As is well appreciated in the art, there are myriad technological obstacles in the identification, enumeration, detection, capture, and isolation of rare cells. These technological obstacles tend to limit the quantitative evaluation of rare cells, for example, in early diagnosis of metastatic diseases and effective monitoring of therapeutic response in patients.
Some rare cells, e.g. circulating tumor cells (CTCs) and/or viable tumor-derived epithelial cells, have been identified in peripheral blood from cancer patients and are likely the origin of intractable metastatic disease. CTCs, as just one type of rare cell, tend to be present in an amount of about 1 CTC per 1 billion blood cells and tend to circulate in peripheral blood of patients with metastatic cancer. Detection, isolation, and capture of CTCs represent a potential alternative to invasive biopsies during diagnosis of disease. More specifically, the ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers, expand the understanding of the biology of metastasis, and improve the therapeutic treatment of cancer patients and the ultimate treatment outcome. Many current strategies for isolating CTCs are limited to complex analytic approaches that are typically very low yield and low purity and that could be improved relative to sensitivity and accuracy.
Many technologies utilize devices through which blood flows over and around large three-dimensional structures for capturing CTCs. These structures tend to be expensive to produce, tend to act as obstacles to the flow of blood thereby decreasing the efficiency of the devices, and tend to lack sensitivity for the CTCs thereby causing the device to have a low cell capture efficiency. In addition, these devices typically face impediments to the release of captured cells, which may be due, at least in part, to the conjugation of antibodies to permanent structures within the devices.
Other technologies utilize microfeatures coated with antibodies, examples of which include the geometrically enhanced differential immunocapture chip (GEDI) chip, the chaotic micromixer HB CTC chip, the high throughput microsampling unit (HTMSU), and the HD-CTC module of an integrated system. These immunocapture devices include features fabricated from polymers, such as polydimethylsiloxane (PDMS), poly(methyl methacrylate) (PMMA), and cyclic olefin copolymer (COC). For capture of rare cells at an early cancer stage as well as during mid-metastasis, however, additional techniques and/or materials may be necessary to enhance sensitivity. Although capture of the rare cells may be accomplished, these technologies are limited with respect to post-capture analysis. This is because release of viable cells from the capture substrate is a challenge.
Accordingly, there remains an opportunity to develop an improved system for detecting rare cells and a method for detecting rare cells in a fluid.